tbuckley/cabot-search huggingface dataset:
P01.10.B EMOTION RECOGNITION IN PATIENTS WITH LOW-GRADE GLIOMA: THE RELATIONSHIP WITH TUMOR LOCATION AND TUMOR VOLUME
Authors: F F Siebenga, H L van der Weide, F Gelmers, S E Rakers, M C A Kramer, R H Enting, I Bosma, A van der Hoorn, H Jeltema, M Wagemakers, R J M Groen, J M Spikman, A M Buunk
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Patients with low-grade gliomas (LGG), generally function well at the time of diagnosis and have a favourable prognosis. However, LGG can have impact on cognitive functioning of patients. To date, little is known about social cognition (SC) in patients with LGG. Social cognitive functions allow the processing of complex social information, with as important element the ability to recognize other people’s emotional expressions. Inaccurate recognition or misinterpretation of emotional facial expressions can lead to impairments in social functioning, which can have adverse effects on quality of life. Therefore, the aim of the present study was to investigate emotion recognition in patients with LGG and the relationship with tumor location and tumor volume. MATERIAL AND METHODS 125 patients with IDH mutated astrocytoma and oligodendroglioma grade 2 and 3, were matched with 169 healthy controls (HC). Tumor location and volume were evaluated pre-radiotherapy based on MRI scans. As a parameter for LGG volume the clinical radiotherapy target volume was used. SC was measured with a test for emotion recognition, i.e. the Facial Expressions of Emotion Stimuli and Tests (FEEST), after surgery. Descriptive statistics and between-group comparisons were performed. RESULTS On a group level, patients with LGG performed significantly lower on the FEEST total score compared to HC. Also, compared to norm data used in clinical practice, 32.8% of the patients showed an impaired performance. Larger LGG volume was significantly associated (p &amp;lt; 0.001) with poorer performance on emotion recognition. However, no direct association between LGG location (frontal, temporal, parietal) and emotion recognition was found. CONCLUSION In patients with LGG, impaired emotion recognition is often present before start of radiotherapy, and is related to larger LGG volume but not to location. Because of the relatively favourable prognosis of patients with LGG, maintaining quality of life is of high importance. Therefore, a thorough neuropsychological examination, including measurements for SC, is necessary to inform patients with LGG about possible changes in SC, and offer appropriate psychoeducation and care.
P03.12.A PHASE III RANDOMIZED TRIAL COMPARING PREOPERATIVE HYPOFRACTIONATED RADIOSURGERY (HSRS) TO POSTOPERATIVE HYPOFRACTIONATED RADIOSURGERY (HSRS) FOR PATIENTS WITH LARGE BRAIN METASTASES SUITABLE FOR SURGICAL RESECTION SUPPORT TRIAL
Authors: P Navarria, F Pessina, E Clerici, L Bellu, S Politi, B Marini, M Riva, B Bono, G Reggiori, L Raspagliesi, M Scorsetti
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Standard of care for patients with large brain metastases (BMs) suitable for surgery is surgical resection followed by radiosurgery in single or multifractions (SRS/HSRS) on tumor bed. Although a satisfactory local control is obtained, an increasing rates of leptomeningeal disease (LMD) related to surgery, and symptomatic radionecrosis related to SRS/HSRS have been observed. In the last years the employ of preoperative SRS/HSRS has been investigated in retrospective studies. Advantages seem to be: better target delineation to intact lesion, reduction of normal brain irradiated considering useless of margins, potential prevention of any cells spilled during resection, greater oxygenation ratio of intact region, sterilization effect, and resection of majority of irradiated tissues. Preoperative HSRS versus postoperative ones will be investigated in multicentric randomized phase III trial. Primary endpoint is rate of leptmeningeal disease secondary endpoints, local control, symptomatic radiation necrosis, surgical morbidity, quality of life (QoL) and neurocognitive functions assessment between the two modalities; brain distant progression (BDP), and overall survival (OS) will be evaluated too. MATERIAL AND METHODS Inclusion criteria are: patients aged 18-80 years, diagnosed malignant primary tumor, KPS≥70, oligometastatic disease, limited brain metastases (up to 4), large BM suitable for surgery. Exclusion criteria are: prior WBRT, SCLC, or germinal cell tumour or Lymphoproliferative disease, prior neurosurgery, and incompatibility to perform MRI. Stratification factors will be: histology of primary tumor (Breast, NSCLC, Melanoma, Other) and BMs location (sovra-or infra-tentorial). In Arm A (experimental) patients undergo preoperative HSRS, 27 Gy in 3 fractions, followed by surgery. In Arm B (control): patients undergo surgical resection followed by postoperative HSRS at the same doses. Outcome evaluation will be assess using MRI, total body CT scan and/or CTPET, neuropsychological and Quality of life assessment before and after treatments. For distinguish RN occurrence and disease progression delayed-contrastMRI, and perfusion MRI will be employed. Considering that estimated 1 year LMD is 10% for postoperative HSRS, and ≤ 2% for preoperative enrolment of 146 patients is expected (73 per Arm). RESULTS Enrollment started at April 2023 and among first patients included the treatment has proven to be safe. CONCLUSION Preoperative HSRS in large BMs suitable for surgical resection need prospective evaluation aiming to improve outcome, and reduced treatments side effects.
P15.05.B THE IMPACT OF IOMRI ON GLIOBLASTOMA RESECTION AND CLINICAL OUTCOMES IN A STATE-OF-THE-ART NEURO-ONCOLOGICAL SETUP
Authors: M Schwendner, W Zhang, S Ille, B Wiestler, B Meyer, S M Krieg
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Intraoperative magnetic resonance imaging (ioMRI) is applied to improve the extent of resection in patients suffering from primary brain tumors, especially glioblastoma (GBM). While some older randomized trials reported data on safety and feasibility, ioMRI’s actual impact in a modern neurosurgical setting has not been sufficiently investigated. We therefore aimed to evaluate the effect of ioMRI on tumor resection and progression-free survival (PFS) in GBM patients in a modern high-volume center. MATERIAL AND METHODS Patients undergoing ioMRI for resection of supratentorial GBM were prospectively included between March 2018 and June 2020. In all cases, ioMRI was performed after complete macroscopic tumor resection. The extent of resection (EOR) was determined by volumetric analysis. Gross total resection (GTR) was defined as EOR ≥95%. Furthermore, progression-free survival (PFS) was analyzed through univariate and multivariate Cox proportional regression analysis. RESULTS Overall, 172 patients were enrolled in this study. The mean EOR increased from 93·9% on ioMRI to 98·3% (p&amp;lt;0·0001) on postoperative MRI, with residual tumor volume decreasing from 1·3 ± 4·2 cm3 to 0·6 ± 2·5 cm3(p=0·0037). The GTR rate increased from 78·5% to 93·0% (p=0·0002). Logistic regression revealed recurrent GBM (odds ratio [OR] =3·047, 95% confidence interval [CI] 1·165-7·974, p=0·023) and tumor volume less than 15 cm3 (OR=3·031, 95% CI 1·062-8·651, p=0·038) as independent risk factors leading to STR. Tumor resection performed additionally after ioMRI lead to equally long PFS compared to patients with complete tumor removal achieved before ioMRI (HR=0·898, 95%CI 0·543-1·483, p=0·67). CONCLUSION ioMRI serves as a valuable tool in a modern neurosurgical setting, severely decreasing residual tumor volume. ioMRI considerably helps to achieve comparable PFS even in cases, where an unexpected tumor residual is found on ioMRI after initial resection.
P09.06.B GAIT CHARACTERISTICS OF PROGRESSIVE DISEASE IN HIGH GRADE GLIOMA: THE BRAINWEAR STUDY
Authors: S Dadhania, M Williams
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Walking is a useful measure of overall health and walking speed has well-documented predictive value for health-related outcomes such as mortality, quality of life, physical and cognitive functional decline in older people. Wearable technology-based gait analysis is emerging as a powerful tool to detect early disease and monitor progression in areas such as Parkinson’s disease. We present an exploratory analysis of gait characteristics at the time of progressive disease from patients with high grade glioma (HGG) participating in the BrainWear Study which evaluates the use of free-living accelerometers in patients with brain tumours. MATERIAL AND METHODS All agreed to wear a wrist-worn Axivity AX3 triaxial accelerometer changed at 14-day intervals. Raw accelerometer data was processed using the UKBiobank OxWearables stepcount model v2.1.2 for Python and inclusion of high-quality wear time selected as ≥72 hours of data in a 7-day data collection and data in each 1-hour period of a 24-hour cycle over multiple days. 12 gait measures were characterised including total daily steps, cadence, cadence peak and minutes walking per day. We analysed variation in gait measures by patient demographics and MRI result. Wilcoxin-signed rank test was used to compare participant gait measures at timepoints of stable disease (SD) or progressive disease (PD). Mixed-effects models were used to evaluate longitudinal changes in gait measures. RESULTS 17 HGG patients (6 female; 11 male) provided 4654 days of accelerometer data across 49 MRI Head scan RESULTS , 32 labelled as PD and 17 as SD. Median age was 62 years (32-79) and mean study participation 273 days (41-550). 8 patients provided accelerometer data at timepoints of both PD and SD allowing for paired analysis. There were no differences in 12 gait measures between age (&amp;lt;60 and &amp;gt;60 years) and gender. In the 6 weeks surrounding an MRI scan, patients with PD walked on average 1856 steps less per day than those with SD, and spent 22 minutes less walking (p=0.0403). Peak 1-minute cadence was 77 steps/min in patients with SD versus 67 steps/min with PD. CONCLUSION The complexity of HGG treatment, recovery and survivorship creates a need for novel monitoring approaches. Wearable accelerometry is feasible and acceptable and evaluating gait measures captures objective evidence of significant differences in patients with PD versus SD. Physical activity measures can guide clinicians in optimising quality of life and may act as an alert system prior to events such as disease progression.
Management of epilepsy during pregnancy and lactation
Authors: Omotola A Hope, Katherine MJ Harris
Journal: BMJ (2023)

ABSTRACT Epilepsy is a group of neurological diseases characterized by susceptibility to recurrent seizures. Antiseizure medications (ASMs) are the mainstay of treatment, but many antiseizure medications with variable safety profiles have been approved for use. For women with epilepsy in their childbearing years, the safety profile is important for them and their unborn children, because treatment is often required to protect them from seizures during pregnancy and lactation. Since no large randomized controlled trials have investigated safety in this subgroup of people with epilepsy, pregnancy registries, cohort and case-control studies from population registries, and a few large prospective cohort studies have played an important role. Valproate, in monotherapy and polytherapy, has been associated with elevated risk of major congenital malformations and neurodevelopmental disorders in children born to mothers who took it. Topiramate and phenobarbital are also associated with elevated risks of congenital malformations and neurodevelopmental disorders, though the risks are lower than those of valproate. Lamotrigine and levetiracetam are relatively safe. Insufficient data exist to reach strong conclusions about the newest antiseizure medications such as eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate. Besides antiseizure medications, other treatments such as vagal nerve stimulation, responsive neurostimulation, and deep brain stimulation are likely safe. In general, breastfeeding does not appear to add any additional long term risks to the child. Creative ways of optimizing registry enrollment and data collection are needed to enhance patient safety.
Irisin reduces amyloid-β by inducing the release of neprilysin from astrocytes following downregulation of ERK-STAT3 signaling
Authors: Eunhee Kim, Hyeonwoo Kim, Mark P. Jedrychowski, Grisilda Bakiasi, Joseph Park, Jane Kruskop, Younjung Choi, Sang Su Kwak, Luisa Quinti, Doo Yeon Kim, Christiane D. Wrann, Bruce M. Spiegelman, Rudolph E. Tanzi, Se Hoon Choi
Journal: Neuron (2023)

A pathological hallmark of Alzheimer's disease (AD) is the deposition of amyloid-β (Aβ) protein in the brain. Physical exercise has been shown to reduce Aβ burden in various AD mouse models, but the underlying mechanisms have not been elucidated. Irisin, an exercise-induced hormone, is the secreted form of fibronectin type-III-domain-containing 5 (FNDC5). Here, using a three-dimensional (3D) cell culture model of AD, we show that irisin significantly reduces Aβ pathology by increasing astrocytic release of the Aβ-degrading enzyme neprilysin (NEP). This is mediated by downregulation of ERK-STAT3 signaling. Finally, we show that integrin αV/β5 acts as the irisin receptor on astrocytes required for irisin-induced release of astrocytic NEP, leading to clearance of Aβ. Our findings reveal for the first time a cellular and molecular mechanism by which exercise-induced irisin attenuates Aβ pathology, suggesting a new target pathway for therapies aimed at the prevention and treatment of AD.
Seasonal light hours modulate peripheral clocks and energy metabolism in mice
Authors: Lewin Small, Leonidas S. Lundell, Jo Iversen, Amy M. Ehrlich, Morten Dall, Astrid L. Basse, Emilie Dalbram, Ann N. Hansen, Jonas T. Treebak, Romain Barrès, Juleen R. Zierath
Journal: Cell Metabolism (2023)

Except for latitudes close to the equator, seasonal variation in light hours can change dramatically between summer and winter. Yet investigations into the interplay between energy metabolism and circadian rhythms typically use a 12 h light:12 h dark photoperiod corresponding to the light duration at the equator. We hypothesized that altering the seasonal photoperiod affects both the rhythmicity of peripheral tissue clocks and energy homeostasis. Mice were housed at photoperiods representing either light hours in summer, winter, or the equinox. Mice housed at a winter photoperiod exhibited an increase in the amplitude of rhythmic lipid metabolism and a modest reduction in fat mass and liver triglyceride content. Comparing melatonin-proficient and -deficient mice, the effect of seasonal light on energy metabolism was largely driven by differences in the rhythmicity of food intake and not melatonin. Together, these data indicate that seasonal light impacts energy metabolism by modulating the timing of eating.
Author Correction: Acquired resistance to a GPRC5D-directed T-cell engager in multiple myeloma is mediated by genetic or epigenetic target inactivation
Authors: Jennifer Derrien, Sarah Gastineau, Antoine Frigout, Nils Giordano, Mia Cherkaoui, Victor Gaborit, Rémi Boinon, Elise Douillard, Magali Devic, Florence Magrangeas, Philippe Moreau, Stéphane Minvielle, Cyrille Touzeau, Eric Letouzé
Journal: Nature Cancer (2023)
The influence of the Great Recession on perinatal health—an ecological study on the trend changes and regional differences in Portugal
Authors: Julia Nadine Doetsch, Ricardo Almendra, Milton Severo, Teresa Leão, Raquel Teixeira, Sandra Marques, Eva Pilot, Thomas Krafft, Henrique Barros
Journal: The Lancet Regional Health - Europe (2023)

Few studies examine the relationship between socioeconomic factors and trends in mortality in high-income European countries. Due to the lack of regional-level data, most recent studies on social inequality in Portugal do not investigate regional differences. This study analyses time trends and regional disparities in the evolution of perinatal mortality (PMR) and infant mortality (IMR) associated with demographic and socioeconomic indicators following Portugal's 2008 economic and financial crisis.Associations were assessed using generalised linear models. A Poisson joinpoint regression model was applied to identify relevant PMR and IMR changes between 2000 and 2018. Country regional disparities were analysed using Mixed Effect Multilevel models.IMR and PMR significantly decreased in the pre-crisis period but not in the post-crisis period. The significant differences between regions in IMR and PMR in 2000 were followed by a different evolution of regional IMR after 2008. PMR and IMR were not significantly associated with socioeconomic indicators. A significant positive association with maternal age at first birth was identified.Results confirm the influence of the crisis on PMR and IMR trends in Portugal, taking into account recurring associations between macroeconomic cycles, variations in mortality trends, macroeconomic volatility, and stagnation of IMR and PMR. Regional inequalities confirm the internal variability of the crisis influence and persistent spatial inequalities affecting IMR patterns.FCT, under the Institute of Public Health of the University of Porto (ISPUP)-EPIUnit (UIDB/04750/2020) and ITR (LA/P/0064/2020), Maastricht University's external PhD programme under the Care and Public Health Research Institute (CAPHRI), and the RECAP preterm project (grant agreement no 733280).
Reducing the risks of nuclear war: the role of health professionals
Authors: Kamran Abbasi, Parveen Ali, Virginia Barbour, Kirsten Bibbins-Domingo, Marcel G M Olde Rikkert, Peng Gong, Andy Haines, Ira Helfand, Richard Horton, Bob Mash, Arun Mitra, Carlos Monteiro, Elena N Naumova, Eric J Rubin, Tilman Ruff, Peush Sahni, James Tumwine, Paul Yonga, Chris Zielinski
Journal:  (2023)
CircXRN2 suppresses tumor progression driven by histone lactylation through activating the Hippo pathway in human bladder cancer
Authors: Bo Xie, Juntao Lin, Xianwu Chen, Xuejian Zhou, Yan Zhang, Mengjing Fan, Jiayong Xiang, Ning He, Zhenghui Hu, Feifan Wang
Journal: Molecular Cancer (2023)

Bladder cancer (BCa) is the fourth most common malignant tumor with a poor prognosis worldwide. Further exploration and research are needed to unmask the underlying roles and molecular mechanisms of circular RNAs. In the current study, our findings showed that circXRN2 suppresses tumor progression driven by histone lactylation by activating the Hippo pathway in human bladder cancer.RNA immunoprecipitation (RIP) followed by circRNA sequencing confirmed circXRN2 as the research object. Overexpression of circXRN2 and knockdown of TAZ/YAP further verified the biological functions in T24 and TCCSUP cells. RIP, immunoprecipitation and coimmunoprecipitation were used to elucidate the interaction between circXRN2 and LATS1. A Seahorse metabolic analyzer was used to determine the glycolytic rate. Cleavage under targets and Tagmentation (CUT&Tag) and chromatin immunoprecipitation (ChIP) were employed to ensure the regulatory roles of H3K18 lactylation in the transcriptional activity of LCN2.CircXRN2 is aberrantly downregulated in bladder cancer tissues and cell lines. CircXRN2 inhibits the proliferation and migration of tumor cells both in vitro and in vivo. In addition, circXRN2 serves as a negative regulator of glycolysis and lactate production. Mechanistically, circXRN2 prevents LATS1 from SPOP-mediated degradation by binding to the SPOP degron and then activates the Hippo signaling pathway to exert various biological functions. The circXRN2-Hippo pathway regulatory axis further modulates tumor progression by inhibiting H3K18 lactylation and LCN2 expression in human bladder cancer.CircXRN2 suppresses tumor progression driven by H3K18 lactylation by activating the Hippo signaling pathway in human bladder cancer. Our results indicated novel therapeutic targets and provided promising strategies for clinical intervention in human bladder cancer.
Endemic parkinsonism: clusters, biology and clinical features
Authors: Katerina Menšíková, John C. Steele, Raymond Rosales, Carlo Colosimo, Peter Spencer, Annie Lannuzel, Yoshikazu Ugawa, Ryogen Sasaki, Santiago Giménez-Roldán, Radoslav Matej, Lucie Tuckova, Dominik Hrabos, Kristyna Kolarikova, Radek Vodicka, Radek Vrtel, Miroslav Strnad, Petr Hlustik, Pavel Otruba, Martin Prochazka, Martin Bares, Susana Boluda, Luc Buee, Gerhard Ransmayr, Petr Kaňovský
Journal: Nature Reviews Neurology (2023)
Selective Antimicrobial Prophylaxis for Vesicoureteral Reflux
Authors: Tej K. Mattoo
Journal: New England Journal of Medicine (2023)

The use of continuous antibiotic prophylaxis in the prevention of urinary tract infection (UTI), particularly in children with vesicoureteral reflux, has been studied extensively during the past 15 years. Double-blind, placebo-controlled trials such as the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial and the Prevention of Recurrent Urinary Tract Infection in Children with Vesicoureteric Reflux and Normal Renal Tracts (PRIVENT) trial showed that continuous antibiotic prophylaxis significantly reduced the risk of UTI among children with vesicoureteral reflux.1,2 However, other randomized trials showed either no beneficial effect3-7 or a beneficial effect that was limited to female patients.8 These variations . . .
Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants
Authors: Beate Kampmann, David Radley, Iona Munjal
Journal: New England Journal of Medicine (2023)

Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain. METHODSIn this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 μg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo.The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth.A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points. RESULTSAt this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point.Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated.Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1).Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion.No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age.The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively). CONCLUSIONSRSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified.